A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Dennis Christensen; Malou Henriksen-Lacey; Arun T Kamath; Thomas Lindenstrøm; Karen S Korsholm; Jan Pravsgaard Christensen; Anne-Francoise Rochat; Paul-Henri Lambert; Peter Andersen; Claire-Anne Siegrist; Yvonne Perrie; Else Marie Agger

doi:10.1016/j.jconrel.2012.03.016

A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Dennis Christensen, Malou Henriksen-Lacey, Arun T Kamath, Thomas Lindenstrøm, Karen S Korsholm, Jan Pravsgaard Christensen, Anne-Francoise Rochat, Paul-Henri Lambert, Peter Andersen, Claire-Anne Siegrist, Yvonne Perrie, Else Marie Agger

LUKKET: Institut for Immunologi og Mikrobiologi

71 Citationer (Scopus)

Abstract

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response.

Originalsprog	Engelsk
Tidsskrift	Journal of controlled release : official journal of the Controlled Release Society
Vol/bind	160
Udgave nummer	3
Sider (fra-til)	468-476
Antal sider	9
DOI	https://doi.org/10.1016/j.jconrel.2012.03.016
Status	Udgivet - 28 jun. 2012

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10.1016/j.jconrel.2012.03.016

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Citationsformater

Christensen, D., Henriksen-Lacey, M., Kamath, A. T., Lindenstrøm, T., Korsholm, K. S., Christensen, J. P., Rochat, A-F., Lambert, P-H., Andersen, P., Siegrist, C-A., Perrie, Y., & Agger, E. M. (2012). A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. Journal of controlled release : official journal of the Controlled Release Society, 160(3), 468-476. https://doi.org/10.1016/j.jconrel.2012.03.016

A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. / Christensen, Dennis; Henriksen-Lacey, Malou; Kamath, Arun T et al.

I: Journal of controlled release : official journal of the Controlled Release Society, Bind 160, Nr. 3, 28.06.2012, s. 468-476.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Christensen, D, Henriksen-Lacey, M, Kamath, AT, Lindenstrøm, T, Korsholm, KS, Christensen, JP, Rochat, A-F, Lambert, P-H, Andersen, P, Siegrist, C-A, Perrie, Y & Agger, EM 2012, 'A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog', Journal of controlled release : official journal of the Controlled Release Society, bind 160, nr. 3, s. 468-476. https://doi.org/10.1016/j.jconrel.2012.03.016

Christensen D, Henriksen-Lacey M, Kamath AT, Lindenstrøm T, Korsholm KS, Christensen JP et al. A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. Journal of controlled release : official journal of the Controlled Release Society. 2012 jun. 28;160(3):468-476. doi: 10.1016/j.jconrel.2012.03.016

Christensen, Dennis ; Henriksen-Lacey, Malou ; Kamath, Arun T et al. / A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. I: Journal of controlled release : official journal of the Controlled Release Society. 2012 ; Bind 160, Nr. 3. s. 468-476.

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abstract = "Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response.",

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T1 - A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

AU - Christensen, Dennis

AU - Henriksen-Lacey, Malou

AU - Kamath, Arun T

AU - Lindenstrøm, Thomas

AU - Korsholm, Karen S

AU - Christensen, Jan Pravsgaard

AU - Rochat, Anne-Francoise

AU - Lambert, Paul-Henri

AU - Andersen, Peter

AU - Siegrist, Claire-Anne

AU - Perrie, Yvonne

AU - Agger, Else Marie

PY - 2012/6/28

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N2 - Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response.

AB - Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response.

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DO - 10.1016/j.jconrel.2012.03.016

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SN - 0168-3659

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JO - Journal of Controlled Release

JF - Journal of Controlled Release

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